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Special Issue "Isolation and Structure Elucidation of Bioactive Compounds (Dedicated to the memory of the late Professor Charles D. Hufford)"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 December 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Muhammad Ilias

National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, Thad Cochran Research Center, University of Mississippi, University, MS 38677, USA
Website | E-Mail
Interests: isolation and structure elucidation of antiinfective; anticancer; chemopreventive; neuroprotective and agrochemical constituents from plants and their use in human and plant health
Guest Editor
Prof. Dr. Charles L. Cantrell

United States Department of Agriculture, Agricultural Research Services, Thad Cochran Research Center, University, MS 38677, USA
Website | E-Mail
Interests: secondary metabolites; isolation and structure elucidation; agrochemical discovery; biopesticides

Special Issue Information

Dear Colleagues,

Throughout the history of mankind, plants have played an indispensible role for the benefit of human health. From ancient folk medicine to modern drugs, dietary supplements and even agrochemicals, the chemistry of plant constituents has become more important for us in understanding life threatening human diseases and chemoprevention practices. The absence of curative drugs in cognitive health has led the worlds aging population toward traditional medicine-based supplements. Isolation and structure determination of these diverse bioactive molecules that only nature can produce, has become a key area for generating new scaffolds for various biological explorations in medicinal chemistry. This is an area currently depleting rapidly due to the disappearance of natural resources. For these reasons, we think it is appropriate to document some recent research in this endeavor.

We wish to dedicate this Special Issue to the memory of the late Professor Charles D. Hufford, a true research pioneer in the fields of natural products and pharmacognosy, who has made immense contributions to the field. Advances in the isolation and structure elucidation, using NMR technology of bioactive compounds, especially secondary plant metabolites, was a passion of Professor Hufford, and therefore, this Special Issue of the journal Molecules has been dedicated to his memory.

Prof. Dr. Muhammad Ilias
Dr. Charles L. Cantrell
Guest Editors

Manuscript Submission Information

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Keywords

  • Secondary metabolites
  • Isolation techniques
  • Structure elucidation
  • Agrochemical discovery
  • Biological activity

Published Papers (21 papers)

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Editorial

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Open AccessEditorial Tribute to the Late Dr. Charles D. Hufford
Molecules 2019, 24(3), 588; https://doi.org/10.3390/molecules24030588
Received: 29 January 2019 / Accepted: 30 January 2019 / Published: 7 February 2019
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Abstract
This Special Issue is dedicated to the late Dr. Charles (Charlie) D. Hufford, former Professor of Pharmacognosy and Associate Dean for Research and Graduate Studies at the University of Mississippi [...] Full article

Research

Jump to: Editorial

Open AccessArticle 4-O-Methylhonokiol Influences Normal Cardiovascular Development in Medaka Embryo
Molecules 2019, 24(3), 475; https://doi.org/10.3390/molecules24030475
Received: 14 December 2018 / Revised: 24 January 2019 / Accepted: 27 January 2019 / Published: 29 January 2019
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Abstract
Although 4-O-Methylhonokiol (MH) effects on neuronal and immune cells have been established, it is still unclear whether MH can cause a change in the structure and function of the cardiovascular system. The overarching goal of this study was to evaluate the [...] Read more.
Although 4-O-Methylhonokiol (MH) effects on neuronal and immune cells have been established, it is still unclear whether MH can cause a change in the structure and function of the cardiovascular system. The overarching goal of this study was to evaluate the effects of MH, isolated from Magnolia grandiflora, on the development of the heart and vasculature in a Japanese medaka model in vivo to predict human health risks. We analyzed the toxicity of MH in different life-stages of medaka embryos. MH uptake into medaka embryos was quantified. The LC50 of two different exposure windows (stages 9–36 (0–6 days post fertilization (dpf)) and 25–36 (2–6 dpf)) were 5.3 ± 0.1 μM and 9.9 ± 0.2 μM. Survival, deformities, days to hatch, and larval locomotor response were quantified. Wnt 1 was overexpressed in MH-treated embryos indicating deregulation of the Wnt signaling pathway, which was associated with spinal and cardiac ventricle deformities. Overexpression of major proinflammatory mediators and biomarkers of the heart were detected. Our results indicated that the differential sensitivity of MH in the embryos was developmental stage-specific. Furthermore, this study demonstrated that certain molecules can serve as promising markers at the transcriptional and phenotypical levels, responding to absorption of MH in the developing embryo. Full article
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Open AccessArticle Biotransformed Metabolites of the Hop Prenylflavanone Isoxanthohumol
Molecules 2019, 24(3), 394; https://doi.org/10.3390/molecules24030394
Received: 30 December 2018 / Revised: 18 January 2019 / Accepted: 20 January 2019 / Published: 22 January 2019
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Abstract
A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in [...] Read more.
A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in the production of three diastereomeric pairs of oxygenated metabolites (27). The microbial metabolites of 1 were formed by epoxidation or hydroxylation of the prenyl group, and HPLC, NMR, and CD analyses revealed that all of the products were diastereomeric pairs composed of (2S)- and (2R)- isomers. The structures of these metabolic compounds were elucidated to be (2S,2″S)- and (2R,2″S)-4′-hydroxy-5-methoxy-7,8-(2,2-dimethyl-3-hydroxy-2,3-dihydro-4H-pyrano)-flavanones (2 and 3), (2S)- and (2R)-7,4′-dihydroxy-5-methoxy-8-(2,3-dihydroxy-3-methylbutyl)-flavanones (4 and 5) which were new oxygenated derivatives, along with (2R)- and (2S)-4′-hydroxy-5-methoxy-2″-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanones (6 and 7) on the basis of spectroscopic data. These results could contribute to understanding the metabolic fates of the major beer prenylflavanone isoxanthohumol that occur in mammalian system. Full article
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Open AccessArticle Terpenes from Zingiber montanum and Their Screening against Multi-Drug Resistant and Methicillin Resistant Staphylococcus aureus
Molecules 2019, 24(3), 385; https://doi.org/10.3390/molecules24030385
Received: 31 December 2018 / Revised: 18 January 2019 / Accepted: 20 January 2019 / Published: 22 January 2019
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Abstract
Bioassay directed isolation of secondary metabolites from the rhizomes of Zingiber montanum (Fam. Zingiberaceae) led to the isolation of mono-, sesqui-, and di-terpenes. The compounds were characterized as (E)-8(17),12-labdadiene-15,16-dial (1), zerumbol (2), zerumbone (3), buddledone [...] Read more.
Bioassay directed isolation of secondary metabolites from the rhizomes of Zingiber montanum (Fam. Zingiberaceae) led to the isolation of mono-, sesqui-, and di-terpenes. The compounds were characterized as (E)-8(17),12-labdadiene-15,16-dial (1), zerumbol (2), zerumbone (3), buddledone A (4), furanodienone (5), germacrone (6), borneol (7), and camphor (8) by analysing one-dimensional (1D) (1H and 13C) and two-dimensional (2D) (COSY, HSQC, HMBC, and NOESY) NMR data and mass spectra. Among these terpenes, compounds 1 and 2 revealed potential antibacterial activity (minimum inhibitory concentrations (MIC) values 32–128 µg/mL; 0.145–0.291 mM)) against a series of clinical isolates of multi-drug resistant (MDR) and Methicillin resistant Staphylococcus aureus (MRSA). Full article
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Open AccessArticle Lignans from the Twigs of Litsea cubeba and Their Bioactivities
Molecules 2019, 24(2), 306; https://doi.org/10.3390/molecules24020306
Received: 18 December 2018 / Revised: 30 December 2018 / Accepted: 4 January 2019 / Published: 16 January 2019
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Abstract
Litsea cubeba, an important medicinal plant, is widely used as a traditional Chinese medicine and spice. Using cytotoxicity-guided fractionation, nine new lignans 19 and ten known analogues 1019 were obtained from the EtOH extract of the twigs of [...] Read more.
Litsea cubeba, an important medicinal plant, is widely used as a traditional Chinese medicine and spice. Using cytotoxicity-guided fractionation, nine new lignans 19 and ten known analogues 1019 were obtained from the EtOH extract of the twigs of L. cubeba. Their structures were assigned by extensive 1D- and 2D-NMR experiments, and the absolute configurations were resolved by specific rotation and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. In the cytotoxicity assay, 7′,9-epoxylignans with feruloyl or cinnamoyl groups (compounds 79, 13 and 14) were selectively cytotoxic against NCI-H1650 cell line, while the dibenzylbutyrolactone lignans 1719 exerted cytotoxicities against HCT-116 and A2780 cell lines. The results highlighted the structure-activity relationship importance of a feruloyl or a cinnamoyl moiety at C-9′ or/and C-7 ketone in 7′,9-epoxylignans. Furthermore, compound 11 was moderate active toward protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 13.5 μM, and compounds 46, 11 and 12 displayed inhibitory activity against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 46.8, 50.1, 58.6, 47.5, and 66.5 μM, respectively. Full article
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Open AccessArticle Tetra-glucopyranosyl Diterpene ent-Kaur-16-en-19-oic Acid and ent-13(S)-Hydroxyatisenoic Acid Derivatives from a Commercial Extract of Stevia rebaudiana (Bertoni) Bertoni
Molecules 2018, 23(12), 3328; https://doi.org/10.3390/molecules23123328
Received: 29 November 2018 / Revised: 13 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
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Abstract
Stevia rebaudiana and its diterpene glycosides are one of the main focuses of food companies interested in developing novel zero calorie sugar substitutes since the recognition of steviol glycosides as Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration. [...] Read more.
Stevia rebaudiana and its diterpene glycosides are one of the main focuses of food companies interested in developing novel zero calorie sugar substitutes since the recognition of steviol glycosides as Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration. Rebaudioside A, one of the major steviol glycosides of the leaves is more than 200 times sweeter than sucrose. However, its lingering aftertaste makes it less attractive as a table-top sweetener, despite its human health benefits. Herein, we report the purification of two novel tetra-glucopyranosyl diterpene glycosides 1 and 3 (rebaudioside A isomers) from a commercial Stevia rebaudiana leaf extract compounds, their saponification products compounds 2 and 4, together with three known compounds isolated in gram quantities. Compound 1 was determined to be 13-[(2-O-β-d-glucopyranosyl-6-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid-β-d-glucopyranosy ester (rebaudioside Z), whereas compound 3 was found to be 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid -β-d-glucopyranosy ester. Two new tetracyclic derivatives with no sugar at position C-19 were prepared from rebaudiosides 1 and 3 under mild alkaline hydrolysis to afford compounds 2 13-[(2-O-β-d-glucopyranosyl-6-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-kaur-16-en-19-oic acid (rebaudioside Z1) and 4 13-[(2-O-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]ent-hydroxyatis-16-en-19-oic acid. Three known compounds were purified in gram quantities and identified as rebaudiosides A (5), H (6) and J (7). Chemical structures were unambiguously elucidated using different approaches, namely HRESIMS, HRESI-MS/MS, and 1D-and 2D-NMR spectroscopic data. Additionally, a high-quality crystal of iso-stevioside was grown in methanol and its structure confirmed by X-ray diffraction. Full article
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Open AccessArticle Fusaproliferin, a Fungal Mycotoxin, Shows Cytotoxicity against Pancreatic Cancer Cell Lines
Molecules 2018, 23(12), 3288; https://doi.org/10.3390/molecules23123288
Received: 17 October 2018 / Revised: 24 November 2018 / Accepted: 4 December 2018 / Published: 11 December 2018
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Abstract
As a part of our ongoing research on endophytic fungi, we have isolated a sesterterpene mycotoxin, fusaproliferin (FUS), from a Fusarium solani strain, which is associated with the plant Aglaonema hookerianum Schott. FUS showed rapid and sub-micromolar IC50 against pancreatic cancer cell [...] Read more.
As a part of our ongoing research on endophytic fungi, we have isolated a sesterterpene mycotoxin, fusaproliferin (FUS), from a Fusarium solani strain, which is associated with the plant Aglaonema hookerianum Schott. FUS showed rapid and sub-micromolar IC50 against pancreatic cancer cell lines. Time-dependent survival analysis and microscopy imaging showed rapid morphological changes in cancer cell lines 4 h after incubation with FUS. This provides a new chemical scaffold that can be further developed to obtain more potent synthetic agents against pancreatic cancer. Full article
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Open AccessArticle Synthesis and Anti-Inflammatory Activities of Phloroglucinol-Based Derivatives
Molecules 2018, 23(12), 3232; https://doi.org/10.3390/molecules23123232
Received: 7 November 2018 / Revised: 30 November 2018 / Accepted: 3 December 2018 / Published: 7 December 2018
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Abstract
The natural product phloroglucinol-based derivatives representing monoacyl-, diacyl-, dimeric acyl-, alkylated monoacyl-, and the nitrogen-containing alkylated monoacylphloro- glucinols were synthesized and evaluated for inhibitory activities against the inflammatory mediators such as inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-κB). The diacylphloroglucinol [...] Read more.
The natural product phloroglucinol-based derivatives representing monoacyl-, diacyl-, dimeric acyl-, alkylated monoacyl-, and the nitrogen-containing alkylated monoacylphloro- glucinols were synthesized and evaluated for inhibitory activities against the inflammatory mediators such as inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-κB). The diacylphloroglucinol compound 2 and the alkylated acylphloroglucinol compound 4 inhibited iNOS with IC50 values of 19.0 and 19.5 µM, respectively, and NF-κB with IC50 values of 34.0 and 37.5 µM, respectively. These compounds may serve as leads for the synthesis of more potent anti-inflammatory compounds for future drug discovery. Full article
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Open AccessFeature PaperArticle Anti-Leishmanial and Cytotoxic Activities of a Series of Maleimides: Synthesis, Biological Evaluation and Structure-Activity Relationship
Molecules 2018, 23(11), 2878; https://doi.org/10.3390/molecules23112878
Received: 25 September 2018 / Revised: 18 October 2018 / Accepted: 31 October 2018 / Published: 5 November 2018
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Abstract
In the present study, 45 maleimides have been synthesized and evaluated for anti-leishmanial activities against L. donovani in vitro and cytotoxicity toward THP1 cells. All compounds exhibited obvious anti-leishmanial activities. Among the tested compounds, there were 10 maleimides with superior anti-leishmanial activities to [...] Read more.
In the present study, 45 maleimides have been synthesized and evaluated for anti-leishmanial activities against L. donovani in vitro and cytotoxicity toward THP1 cells. All compounds exhibited obvious anti-leishmanial activities. Among the tested compounds, there were 10 maleimides with superior anti-leishmanial activities to standard drug amphotericin B, and 32 maleimides with superior anti-leishmanial activities to standard drug pentamidine, especially compounds 16 (IC50 < 0.0128 μg/mL) and 42 (IC50 < 0.0128 μg/mL), which showed extraordinary efficacy in an in vitro test and low cytotoxicities (CC50 > 10 μg/mL). The anti-leishmanial activities of 16 and 42 were 10 times better than that of amphotericin B. The structure and activity relationship (SAR) studies revealed that 3,4-non-substituted maleimides displayed the strongest anti-leishmanial activities compared to those for 3-methyl-maleimides and 3,4-dichloro-maleimides. 3,4-dichloro-maleimides were the least cytotoxic compared to 3-methyl-maleimides and 3,4-non-substituted maleimides. The results show that several of the reported compounds are promising leads for potential anti-leishmanial drug development. Full article
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Open AccessArticle Antibacterial Activities of Metabolites from Vitis rotundifolia (Muscadine) Roots against Fish Pathogenic Bacteria
Molecules 2018, 23(11), 2761; https://doi.org/10.3390/molecules23112761
Received: 18 September 2018 / Revised: 21 October 2018 / Accepted: 22 October 2018 / Published: 25 October 2018
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Abstract
Enteric septicemia of catfish, columnaris disease and streptococcosis, caused by Edwardsiella ictaluri, Flavobacterium columnare and Streptococcus iniae, respectively, are the most common bacterial diseases of economic significance to the pond-raised channel catfish Ictalurus punctatus industry. Certain management practices are used by [...] Read more.
Enteric septicemia of catfish, columnaris disease and streptococcosis, caused by Edwardsiella ictaluri, Flavobacterium columnare and Streptococcus iniae, respectively, are the most common bacterial diseases of economic significance to the pond-raised channel catfish Ictalurus punctatus industry. Certain management practices are used by catfish farmers to prevent large financial losses from these diseases such as the use of commercial antibiotics. In order to discover environmentally benign alternatives, using a rapid bioassay, we evaluated a crude extract from the roots of muscadine Vitis rotundifolia against these fish pathogenic bacteria and determined that the extract was most active against F. columnare. Subsequently, several isolated compounds from the root extract were isolated. Among these isolated compounds, (+)-hopeaphenol (2) and (+)-vitisin A (3) were found to be the most active (bacteriostatic activity only) against F. columnare, with 24-h 50% inhibition concentrations of 4.0 ± 0.7 and 7.7 ± 0.6 mg/L, respectively, and minimum inhibitory concentrations of 9.1 ± 0 mg/L for each compound which were approximately 25X less active than the drug control florfenicol. Efficacy testing of 2 and 3 is necessary to further evaluate the potential for these compounds to be used as antibacterial agents for managing columnaris disease. Full article
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Open AccessArticle Essential Oils of Five Baccharis Species: Investigations on the Chemical Composition and Biological Activities
Molecules 2018, 23(10), 2620; https://doi.org/10.3390/molecules23102620
Received: 7 August 2018 / Revised: 3 October 2018 / Accepted: 10 October 2018 / Published: 12 October 2018
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Abstract
This paper provides a comparative account of the essential oil chemical composition and biological activities of five Brazilian species of Baccharis (Asteraceae), namely B. microdonta, B. pauciflosculosa, B. punctulata, B. reticularioides, and B. sphenophylla. The chemical compositions of [...] Read more.
This paper provides a comparative account of the essential oil chemical composition and biological activities of five Brazilian species of Baccharis (Asteraceae), namely B. microdonta, B. pauciflosculosa, B. punctulata, B. reticularioides, and B. sphenophylla. The chemical compositions of three species (B. pauciflosculosa, B. reticularioides, and B. sphenophylla) are reported for the first time. Analyses by GC/MS showed notable differences in the essential oil compositions of the five species. α-Pinene was observed in the highest concentration (24.50%) in B. reticularioides. Other major compounds included α-bisabolol (23.63%) in B. punctulata, spathulenol (24.74%) and kongol (22.22%) in B. microdonta, β-pinene (18.33%) and limonene (18.77%) in B. pauciflosculosa, and β-pinene (15.24%), limonene (14.33%), and spathulenol (13.15%) in B. sphenophylla. In vitro analyses for antimalarial, antitrypanosomal, and insecticidal activities were conducted for all of the species. B. microdonta and B. reticularioides showed good antitrypanosomal activities; B. sphenophylla showed insecticidal activities in fumigation bioassay against bed bugs; and B. pauciflosculosa, B. reticularioides, and B. sphenophylla exhibited moderate antimalarial activities. B. microdonta and B. punctulata showed cytotoxicity. The leaves and stems of all five species showed glandular trichomes and ducts as secretory structures. DNA barcoding successfully determined the main DNA sequences of the investigated species and enabled authenticating them. Full article
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Open AccessArticle Isolation and Identification of the Five Novel Flavonoids from Genipa americana Leaves
Molecules 2018, 23(10), 2521; https://doi.org/10.3390/molecules23102521
Received: 15 August 2018 / Revised: 3 September 2018 / Accepted: 5 September 2018 / Published: 2 October 2018
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Abstract
Genipa americana is a medicinal plant popularly known as “jenipapo”, which occurs in Brazil and belongs to the Rubiaceae family. It is a species widely distributed in the tropical Central and South America, especially in the Cerrado biome. Their leaves and fruits are [...] Read more.
Genipa americana is a medicinal plant popularly known as “jenipapo”, which occurs in Brazil and belongs to the Rubiaceae family. It is a species widely distributed in the tropical Central and South America, especially in the Cerrado biome. Their leaves and fruits are used as food and popularly in folk medicine to treat anemias, as an antidiarrheal, and anti-syphilitic. Iridoids are the main secondary metabolites described from G. americana, but few studies have been conducted with their leaves. In this study, the aim was to chemical approach for identify the main compounds present at the extract of G. americana leaves. The powdered leaves were extracted by maceration with EtOH: water (70:30, v/v), following liquid-liquid partition with petroleum ether, chloroform, ethyl acetate and n-butanol. A total of 13 compounds were identified. In addition three flavonoids were isolated from the ethyl acetate fraction: quercetin-3-O-robinoside (GAF 1), kaempferol-3-O-robinoside (GAF 2) and isorhamnetin-3-O-robinoside (GAF 3) and, from n-butanol fraction more two flavonoids were isolated, kaempferol-3-O-robinoside-7-O-rhamnoside (robinin) (GAF 4) and isorhamnetin-3-O-robinoside-7-rhamnoside (GAF 5). Chemical structures of these five flavonoids were elucidated using spectroscopic methods (MS, 1H and 13C-NMR 1D and 2D). These flavonoids glycosides were described for the first time in G. americana. Full article
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Open AccessArticle New Chromones from a Marine-Derived Fungus, Arthrinium sp., and Their Biological Activity
Molecules 2018, 23(8), 1982; https://doi.org/10.3390/molecules23081982
Received: 15 July 2018 / Revised: 5 August 2018 / Accepted: 8 August 2018 / Published: 9 August 2018
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Abstract
Five new chromone derivatives, arthones A–E (15), together with eight known biogenetically related cometabolites (613), were isolated from a deep-sea-derived fungus Arthrinium sp. UJNMF0008. Their structures were assigned by detailed analyses of spectroscopic data, while [...] Read more.
Five new chromone derivatives, arthones A–E (15), together with eight known biogenetically related cometabolites (613), were isolated from a deep-sea-derived fungus Arthrinium sp. UJNMF0008. Their structures were assigned by detailed analyses of spectroscopic data, while the absolute configurations of 1 and 5 were established by electronic circular dichroism (ECD) calculations and that of 2 was determined by modified Mosher ester method. Compounds 3 and 8 exhibited potent antioxidant property with DPPH and ABTS radical scavenging activities, with IC50 values ranging from 16.9 to 18.7 μM. Meanwhile, no compounds indicated obvious bioactivity in our antimicrobial and anti-inflammatory assays at 50.0 μM. Full article
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Open AccessArticle Flavonoids, Sterols and Lignans from Cochlospermum vitifolium and Their Relationship with Its Liver Activity
Molecules 2018, 23(8), 1952; https://doi.org/10.3390/molecules23081952
Received: 13 July 2018 / Revised: 2 August 2018 / Accepted: 3 August 2018 / Published: 5 August 2018
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Abstract
The sterols β-sitostenone (1), stigmast-4,6,8(14),22-tetraen-3-one (2), β-sitosterol (3) and stigmasterol (4), the aromatic derivatives antiarol (5) and gentisic acid (6), the phenylpropanes coniferyl alcohol (7), epoxyconiferyl alcohol (8 [...] Read more.
The sterols β-sitostenone (1), stigmast-4,6,8(14),22-tetraen-3-one (2), β-sitosterol (3) and stigmasterol (4), the aromatic derivatives antiarol (5) and gentisic acid (6), the phenylpropanes coniferyl alcohol (7), epoxyconiferyl alcohol (8) and ferulic acid (9), the apocarotenoid vomifoliol (10), the flavonoids naringenin (11), 7,4′-dimethoxytaxifolin (7,4′-dimethoxydihydroquercetin, 12), aromadendrin (13), kaempferol (14), taxifolin (dihydroquercetin, 15), prunin (naringenin-7-O-β-d-glucoside, 16), populnin (kaempferol-7-O-β-d-glucoside, 17) and senecin (aromadendrin-7-O-β-d-glucoside, 18) and the lignans kobusin (19) and pinoresinol (20), were isolated from the dried bark of Cochlospermum vitifolium Spreng (Cochlospermaceae), a Mexican medicinal plant used to treat jaundice, liver ailments and hepatitis C. Fourteen of these compounds were isolated for the first time from this plant and from the Cochlospermum genus. Compounds 34, 67, 911, 1317 and 20 have previously exhibited diverse beneficial liver activities. The presence of these compounds in C. vitifolium correlates with the use of this Mexican medicinal plant. Full article
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Open AccessArticle The Phytochemical and Biological Investigation of Jatropha pelargoniifolia Root Native to the Kingdom of Saudi Arabia
Molecules 2018, 23(8), 1892; https://doi.org/10.3390/molecules23081892
Received: 29 May 2018 / Revised: 19 July 2018 / Accepted: 25 July 2018 / Published: 28 July 2018
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Abstract
Extensive phytochemical analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) has resulted in the isolation and identification of 22 secondary metabolites. 6-hydroxy-8-methoxycoumarin-7-O-β-d-glycopyranoside (15) and 2-hydroxymethyl N-methyltryptamine (18) were isolated and identified as [...] Read more.
Extensive phytochemical analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) has resulted in the isolation and identification of 22 secondary metabolites. 6-hydroxy-8-methoxycoumarin-7-O-β-d-glycopyranoside (15) and 2-hydroxymethyl N-methyltryptamine (18) were isolated and identified as new compounds along with the known diterpenoid (1, 3, 4, and 7), triterpenoid (2 and 6), flavonoid (5, 11, 13, 14, and 16), coumarinolignan (810), coumarin (15), pyrimidine (12), indole (17, 18), and tyramine-derived molecules (1922). The anti-inflammatory, analgesic, and antipyretic activities were evaluated for fifteen of the adequately available isolated compounds (16, 811, 13, 14, 16, 21, and 22). Seven (4, 6, 10, 5, 13, 16, and 22) of the tested compounds showed a significant analgesic effect ranging from 40% to 80% at 10 mg/kg in two in vivo models. Compound 1 could also prove its analgesic property (67.21%) when it was evaluated on a third in vivo model at the same dose. The in vitro anti-inflammatory activity was also recorded where all compounds showed the ability to scavenge nitric oxide (NO) radical in a dose-dependent manner. However, eight compounds (1, 4, 5, 6, 10, 13, 16, and 22) out of the fifteen tested compounds exhibited considerable in vivo anti-inflammatory activity which reached 64.91% for compound 10 at a dose of 10 mg/kg. Moreover, the tested compounds exhibited an antipyretic effect in a yeast-induced hyperthermia in mice. The activity was found to be highly pronounced with compounds 1, 5, 6, 10, 13, and 16 which decreased the rectal temperature to about 37 °C after 2 h of the induced hyperthermia (~39 °C) at a dose of 10 mg/kg. This study could provide scientific evidence for the traditional use of J. pelargoniifolia as an anti-inflammatory, analgesic, and antipyretic. Full article
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Open AccessArticle Preparation and Characterization of Resveratrol Loaded Pectin/Alginate Blend Gastro-Resistant Microparticles
Molecules 2018, 23(8), 1886; https://doi.org/10.3390/molecules23081886
Received: 5 July 2018 / Revised: 24 July 2018 / Accepted: 27 July 2018 / Published: 28 July 2018
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Abstract
Background: The use of resveratrol as a dietary supplement is limited because it is easily oxidized and, after oral ingestion, it is metabolized into enterocytes and hepatocytes. Thus, new formulations are needed in order to improve its oral bioavailability. Objective: The objective of [...] Read more.
Background: The use of resveratrol as a dietary supplement is limited because it is easily oxidized and, after oral ingestion, it is metabolized into enterocytes and hepatocytes. Thus, new formulations are needed in order to improve its oral bioavailability. Objective: The objective of this study was to develop and characterize a gastro-resistant formulation of resveratrol for oral administration as a dietary supplement. Method: Resveratrol was encapsulated in Eudragit-coated pectin-alginate microparticles. Results: The microparticle size was about 1450 µm, with an encapsulation efficiency of 41.72% ± 1.92%. The dissolution assay conducted, as specified in the European Pharmacopoeia for delayed-release dosage forms, revealed that our microparticles were gastro-resistant, because the resveratrol percentage released from microparticles in acid medium was less than 10%. In addition, the high-performance liquid chromatographic (HPLC) method developed for resveratrol content quantification in the microparticles was validated according to International Council for Harmonisation (ICH) Q2 (R1) guidelines. Finally, the biological activity of resveratrol was investigated in 3T3-L1 mature adipocytes, concluding that the encapsulation process does not affect the activity of resveratrol. Conclusion: In summary, the gastro-resistant microparticles developed could represent a suitable method of including resveratrol in dietary supplements and in functional foods used in obesity therapy. Full article
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Open AccessArticle Efficacy of Prosopilosidine from Prosopis glandulosa var. glandulosa against Cryptococcus neoformans Infection in a Murine Model
Molecules 2018, 23(7), 1674; https://doi.org/10.3390/molecules23071674
Received: 1 June 2018 / Revised: 29 June 2018 / Accepted: 6 July 2018 / Published: 10 July 2018
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Abstract
In this study, 2,3-dihydro-1H-indolizinium alkaloid-prosopilosidine (PPD), that was isolated from Prosopis glandulosa, was evaluated against C. neoformans in a murine model of cryptococcosis. In vitro and in vivo toxicity of indolizidines were also evaluated. Mice were infected via the tail [...] Read more.
In this study, 2,3-dihydro-1H-indolizinium alkaloid-prosopilosidine (PPD), that was isolated from Prosopis glandulosa, was evaluated against C. neoformans in a murine model of cryptococcosis. In vitro and in vivo toxicity of indolizidines were also evaluated. Mice were infected via the tail vein with live C. neoformans. Twenty-four hours post-infection, the mice were treated with PPD once a day (i.p.) or twice a day (bid) orally, or with amphotericin B (Amp B) intraperitoneally (IP), or with fluconazole (Flu) orally for 5 days. The brains of all of the animals were aseptically removed and the numbers of live C. neoformans were recovered. In vitro toxicity of indolizidine alkaloids was determined in HepG2 cells. PPD showed to be potent in vivo activity against C. neoformans at a dose of 0.0625 mg/kg by eliminating ~76% of the organisms compared to ~83% with Amp B (1.5 mg/kg). In addition, PPD was found to be equally efficacious, but less toxic, at either 0.125 or 0.0625 mg/kg compared to Amp B (1.5 mg/kg) when it was administered bid (twice a day) by an i.p. route. When tested by an oral route, PPD (10 mg/kg) showed potent activity in this murine model of cryptococcosis with ~82% of organisms eliminated from the brain tissue, whereas Flu (15 mg/kg) reduced ~90% of the infection. In vitro results suggest that quaternary indolizidines were less toxic as compared to those of tertiary bases. PPD (20 mg/kg) did not cause any alteration in the plasma chemistry profiles. These results indicated that PPD was active in eliminating cryptococcal infection by oral and i.p. routes at lower doses compared to Amp B. or Flu. Full article
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Open AccessArticle N-oxide alkaloids from Crinum amabile (Amaryllidaceae)
Molecules 2018, 23(6), 1277; https://doi.org/10.3390/molecules23061277
Received: 9 April 2018 / Revised: 23 May 2018 / Accepted: 24 May 2018 / Published: 26 May 2018
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Abstract
Natural products play an important role in the development of new drugs. In this context, the Amaryllidaceae alkaloids have attracted considerable attention in view of their unique structural features and various biological activities. In this study, twenty-three alkaloids were identified from Crinum amabile [...] Read more.
Natural products play an important role in the development of new drugs. In this context, the Amaryllidaceae alkaloids have attracted considerable attention in view of their unique structural features and various biological activities. In this study, twenty-three alkaloids were identified from Crinum amabile by GC-MS and two new structures (augustine N-oxide and buphanisine N-oxide) were structurally elucidated by NMR. Anti-parasitic and cholinesterase (AChE and BuChE) inhibitory activities of six alkaloids isolated from this species, including the two new compounds, are described herein. None of the alkaloids isolated from C. amabile gave better results than the reference drugs, so it was possible to conclude that the N-oxide group does not increase their therapeutic potential. Full article
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Open AccessArticle MS/MS-Guided Isolation of Clarinoside, a New Anti-Inflammatory Pentalogin Derivative
Molecules 2018, 23(5), 1237; https://doi.org/10.3390/molecules23051237
Received: 30 March 2018 / Revised: 10 May 2018 / Accepted: 19 May 2018 / Published: 22 May 2018
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Abstract
Re-investigation of the chemical composition of the annual plant Mitracarpus scaber Zucc. led to the identification of clarinoside, a new pentalogin derivative containing a rare quinovose moiety, and the known compound harounoside. While the planar structure was fully determined using tandem mass spectrometry [...] Read more.
Re-investigation of the chemical composition of the annual plant Mitracarpus scaber Zucc. led to the identification of clarinoside, a new pentalogin derivative containing a rare quinovose moiety, and the known compound harounoside. While the planar structure was fully determined using tandem mass spectrometry (MS) and quantum mechanics (QM) calculations, the tridimensional structure was unravelled after isolation and NMR analysis. The absolute configuration was assigned by comparison of experimental and theoretical synchrotron radiation circular dichroism spectra. Both compounds were tested for anti-inflammatory activity, and compound 1 showed the ability to inhibit the production of interleukin-8 (Il-8) with an IC 50 value of 9.17 μ M. Full article
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Open AccessArticle A Chemical Investigation of the Leaves of Morus alba L.
Molecules 2018, 23(5), 1018; https://doi.org/10.3390/molecules23051018
Received: 31 March 2018 / Revised: 21 April 2018 / Accepted: 24 April 2018 / Published: 26 April 2018
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Abstract
The leaves of Morus alba L. are an important herbal medicine in Asia. The systematic isolation of the metabolites of the leaves of Morus alba L. was achieved using a combination of liquid chromatography techniques. The structures were elucidated by spectroscopic data analysis [...] Read more.
The leaves of Morus alba L. are an important herbal medicine in Asia. The systematic isolation of the metabolites of the leaves of Morus alba L. was achieved using a combination of liquid chromatography techniques. The structures were elucidated by spectroscopic data analysis and the absolute configuration was determined based on electronic circular dichroism (ECD) spectroscopic data and hydrolysis experiments. Their biological activity was evaluated using different biological assays, such as the assessment of their capacity to inhibit the aldose reductase enzyme; the determination of their cytotoxic activity and the evaluation of their neuroprotective effects against the deprivation of serum or against the presence of nicouline. Chemical investigation of the leaves of Morus alba L. resulted in four new structures 14 and a known molecule 5. Compounds 2 and 5 inhibited aldose reductase with IC50 values of 4.33 μM and 6.0 μM compared with the potent AR inhibitor epalrestat (IC50 1.88 × 10−3 μM). Pretreatment with compound 3 decreased PC12 cell apoptosis subsequent serum deprivation condition and pretreatment with compound 5 decreased nicouline-induced PC12 cell apoptosis as compared with control cells (p < 0.001). Full article
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Open AccessArticle Microbial Oxidation of the Fusidic Acid Side Chain by Cunninghamella echinulata
Molecules 2018, 23(4), 970; https://doi.org/10.3390/molecules23040970
Received: 10 April 2018 / Revised: 17 April 2018 / Accepted: 20 April 2018 / Published: 21 April 2018
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Abstract
Biotransformation of fusidic acid (1) was accomplished using a battery of microorganisms including Cunninghamella echinulata NRRL 1382, which converted fusidic acid (1) into three new metabolites 24 and the known metabolite 5. These metabolites were identified [...] Read more.
Biotransformation of fusidic acid (1) was accomplished using a battery of microorganisms including Cunninghamella echinulata NRRL 1382, which converted fusidic acid (1) into three new metabolites 24 and the known metabolite 5. These metabolites were identified using 1D and 2D NMR and HRESI-FTMS data. Structural assignment of the compounds was supported via computation of 1H- and 13C-NMR chemical shifts. Compounds 2 and 3 were assigned as the 27-hydroxy and 26-hydroxy derivatives of fusidic acid, respectively. Subsequent oxidation of 3 afforded aldehyde 4 and the dicarboxylic acid 5. Compounds 2, 4 and 5 were screened for antimicrobial activity against different Gram positive and negative bacteria, Mycobacterium smegmatis, M. intercellulare and Candida albicans. The compounds showed lower activity compared to fusidic acid against the tested strains. Molecular docking studies were carried out to assist the structural assignments and predict the binding modes of the metabolites. Full article
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